LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model

This randomized, double-blind, placebo-controlled, crossover study (n=24) investigated the subjective effects of LSD (50 μg) and found significant overlap in the phenomenology of psychotic, mystical, and ego-dissolving experiences. The authors highlight the importance of meaning attribution to psychotic experiences in explaining how these different constructs converge in mystical experiences.


Background: For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience.

Methods: In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 μg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined.

Results: LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience.

Conclusions: The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.

Authors: Isabel Wießner, Marcelo Falchi, Fernanda Palhano-Fontes, Amanda Feilding, Sidarta Ribeiro & Luís Fernando Tófoli


Research on LSD is notoriously multifaceted as scientists have characterized its subjective as either psychosis-like, mystical, or mind-revealing across various stages of its historic development. In fact, Humphrey Osmond who coined the term ‘psychedelic’ in conjunction with Aldous Huxley, sparked his interest in the substance upon noticing that it induces similar effects as the symptoms of schizophrenia. And although many researchers were interested in utilizing the mind-manifesting psychedelic properties of the substance to treat alcoholism and mood disorders, these research efforts were undercut by the cultural shift which propagated the myth that psychedelics can induce psychosis. Although this myth is largely discredited, the psychotomimetic model remains one of the most well-studied paradigms that compares the similarities and differences between psychedelics and psychosis (Geyer & Vollenweider, 2008).

As the word psychotomimetic implies, psychedelics mimic some of the most salient features of psychosis, such as altered perception of senses, self, body, time, altered emotions, impaired cognition, loss of intentionality, magical thinking, among others. But given the proximity of these symptoms to a state of psychosis, how is it that the same subjective effects take up such a central role within psychedelic-assisted psychotherapy? The current study sought to address this nuanced issue by examining how low-dose LSD (50 μg) occasions these experiences within the same cohort, in order to investigate the relationships that underly these different constructs within a randomized, double-blind, placebo-controlled, crossover study.

What did they measure?

  • Psychotic experiences were assessed within the model of aberrant salience, which is broadly defined as the process of placing inappropriate significance toexternal objects or internal representations, which gives rise to hallucinations and delusions in psychotic phenomena
  • Therapeutic potential was assessed by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ)
  • Psychedelic experiences were assessed assessed with four questionnaires: Altered State of Consciousness Questionnaire, Mystical Experiences Questionnaire, Challenging Experiences Questionnaire, and the Ego-Dissolution Inventory

What was the relationship between these experiences?

  • LSD-induced aberrant salience which highly correlated with altered state of consciousness, mystical experiences, and ego-dissolution
  • LSD increased suggestibility but not mindfulness

What does this reveal?

The results suggest that psychedelic and psychotic experiences share a mystical and ego-dissolution phenomenology. LSD spontaneously increased psychosis-like attributes to a greater extent than therapy-related aspects in the psychedelic experiences, which points to common mechanisms. LSD also increased suggestibility but not mindfulness, which indicates that substance does not have intrinsically therapeutic properties, but that therapeutic processes are engendered via therapeutic suggestion.

The authors also suggest a similar mechanism for LSD-induced aberrant salience, which might increase significance attribution and reduce ego boundaries and defence mechanisms, allowing for therapeutic changes in perspectives and attitudes. Hence the process of meaning attribution may elevate psychosis-like phenomena through therapeutic suggestions that foster mystical experiences.



Psychedelics have been investigated as models of psychosis and as therapeutic models for depression, anxiety, and substance use disorders.

In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 g D-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience, therapeutic potential, and psychedelic experience were assessed.

LSD increased aberrant salience and suggestibility, but not mindfulness, and these effects correlated with aspects of psychedelic experience.

The LSD state resembles a psychotic experience, and therapeutic suggestions fostering mystical experiences might be helpful.


Since the discovery of its psychedelic properties, LSD has carried a paradoxical history. This study sought to bridge the gap between these parallel research lines by examining key parameters of both areas.

Regarding the psychosis model, salience processing is a key factor in the generation of psychotic experiences, including altered perception of senses, self, body, time, altered emotions, impaired cognition, loss of intentionality, magical thinking, among other behavioral and neurophysiological phenomena.

Aberrant salience is related to hallucinations, delusions, and negative symptoms in schizophrenia, first-episode psychosis, and healthy controls, and increases with cannabis use. It also mediates the cannabis-induced development of schizotypal symptoms.

Regarding the therapeutic model, psychedelic-induced suggestibility and mindfulness seem to be promising approaches to date. These approaches might potentially boost treatment efficiency in cases of pain, anxiety, somatization, asthma, and nicotine addiction.

This study explored the effects of LSD on mindfulness and suggested that LSD increases aberrant salience, suggestibility, and mindfulness, and that there are positive correlations between LSD-induced aberrant salience, suggestibility, mindfulness, and psychedelic experience.

Study design

This study used a randomized, double-blind, placebo-controlled, crossover design and was approved by the University Research Ethics Committee and the National Health Surveillance Agency.


Twenty-five healthy participants were recruited in a convenience sample. They provided written informed consent before participation, and were subject to screening for psychiatric symptoms, heart disease, and non-native speaking of Brazilian Portuguese.


Participants received 50 g LSD or inactive placebo (alcohol solution) orally diluted in 30 ml water. The dose was chosen to minimize the risk of adverse reactions and exert noticeable effects without impairing the subjects’ ability to complete the measurements.

Psychedelic experience

Subjective intensity and valence of drug effects were assessed by visual analog scales. Maximum intensity, maximum and minimum valence, area under the curve for intensity, and positive and negative valence were calculated.

The LSD-induced experience was self-rated using the Brazilian Portuguese versions of the Altered State of Consciousness Questionnaire (ASC), Mystical Experiences Questionnaire (MEQ), Challenging Experiences Questionnaire (CEQ), and Ego-Dissolution Inventory (EDI).

Aberrant salience

The Aberrant Salience Inventory measures the trait aberrant salience using 29 items in yes – no format. The scale was adapted to a state scale by converting items from present tense to past tense.


The Creative Imagination Scale (CIS) measures suggestibility and contains 10 items of different modalities. The scale was translated by our team and split into two parallel versions, which were balanced across participants and counterbalanced across treatments.


Mindfulness was measured by the Five Facet Mindfulness Questionnaire, Mindful Attention Awareness Scale, and Experiences Questionnaire. All scales were applied before drug administration, 24 h afterward, and 2 weeks afterward.

Study procedures

Two investigators were present at each study session, a psychologist and a psychiatrist. They were continuously available for questions and doubts via e-mail and phone.

The session started at 7:30 a.m. with baseline measurements, followed by diverse tests and questionnaires throughout the day. After the session, the subject returned to complete measurements of mindfulness and aberrant salience, and was released around 10:00 a.m.

Participants completed online follow-up measurements including mindfulness scales two weeks and four months after the second session. No persisting side effects were reported.

Data analysis

Statistical analysis was performed with IBM SPSS Statistics (version 22). Results were Bonferroni-corrected post hoc for multiple comparisons unless stated otherwise, and Spearman’s rank correlation coefficients were calculated between LSD-induced changes on psychedelic experience, aberrant salience, suggestibility, and mindfulness.

Psychedelic experience

LSD increased intensity and positive valence compared to placebo, and there was a significant period effect for IntAUC. There were no other effects of period and carryover.

The ASC and MEQ were significantly higher under LSD than placebo in Total and all factors except Anxiety, and the CEQ was significantly higher under LSD than placebo in Total, Grief, Physical Distress, Insanity, and Isolation.

Aberrant salience

Under LSD, ASI scores were significantly higher compared to placebo, with no effects of period or carryover.


Under LSD, CIS ratings were significantly increased compared to placebo, and increases were observed in Extern Ambience, Weight, Sensation, and Taste, but not Intern Ambience.


Regarding aberrant salience, psychedelic experiences were positively correlated with mindfulness at T1 but negatively with mindfulness at T2. Furthermore, suggestibility was not correlated with other LSD-induced effects.


This study explored the relationship between psychedelic experiences and aberrant salience, suggestibility, mindfulness and the psychosis model. It found that psychedelic experiences were positively correlated with aberrant salience and suggestibility at T1 but negatively correlated with mindfulness at T2.

Psychedelic experience

A low dose of LSD (50 g) induces predominantly positive emotions, including increased positive valence, Positive Mood, only slightly increased Grief, Physical Distress, Insanity, and Isolation, and unaltered negative valence, Anxiety, Fear, Death, and Paranoia. This dose also induces mystical experiences and ego-dissolution, which might support an altered perspective on the self.

Psychosis model

LSD increases all aberrant salience factors, including Senses Sharpening, Impending Understanding, Increased Significance, Heightened Emotionality, and Heightened Cognition. However, emotional aspects of aberrant salience and psychedelic experience showed few correlations, pointing to the limits of the psychosis model.

Altogether, our findings highlight the potential of low psychedelic doses to induce psychotic-like, meaning-laden experiences, including hallucinations and delusions. Furthermore, aberrant salience might provide an intriguing perspective to explain psychedelic phenomena including altered cognition, logical thinking, self- and other-perception, empathy, and prosocial attitudes.

Therapy model

LSD increased suggestibility in a manner similar to previous results, and the modulated Extern Ambience indicates application potential for mood disorders, somatization, pain, and eating disorders. However, psychedelic-induced suggestibility needs to be prudently applied, since suggestions can engender potentially harmful results.

In contrast to previous findings, LSD did not increase mindfulness. This might be explained by setting or placebo effects, or by substance differences, such as the different psychoactive components of ayahuasca, toad secretion, and mushrooms.

Connecting psychedelic experience, psychosis model, and therapy model

Suggestibility was not correlated with other effects, and mindfulness changes were correlated with mystical experiences and ego-dissolution, positively in the short term and negatively in the mid-term.

Aberrant salience showed no correlations with suggestibility or mindfulness, but robustly correlated with mystical and ego-dissolution experiences, which are fundamental within psychedelic-assisted treatments and psychotic experiences.

In some non-Western cultures, mystical and psychotic experiences are reframed as spiritual trance and shamanism, and psychedelic use in shamanic rituals and psychedelic-assisted psychotherapy underlies different conceptions of illness and healing. Therefore, mystical experiences might constitute the link between the psychosis model and therapy model.


Several limitations should be considered when interpreting the results, such as the difficulty of blinding, imbalanced education levels across groups, and lack of drug screening. Moreover, future research should specify how mystical experiences are comparable in quality and quantity within the psychosis model and therapy model.


This study explored the use of low dose LSD as a psychosis model and therapeutic tool. It found that LSD increased suggestibility but not mindfulness, and increased aberrant salience, suggesting a greater weight of psychosis- than therapy-related aspects in the psychedelic phenomenology.

Author contributions: IW designed and coordinated the study, MF conducted clinical interviews, FPF contributed to data analysis, and LFT reviewed the manuscript.

Conflict of interest. None.

1 Other similarities between schizophrenia and bipolar disorder include distorted perception of senses, time, space, self, and body, thought disturbances, perceived loss of control, reduced organization and adjustment of behavior, impaired cognition, disorganized language, and several neurophysiological parameters. Most studies compared psychedelic effects in healthy subjects to experiences of patients with psychotic disorders. Interestingly, a number of studies administered psychedelics to patients with schizophrenia or people with predisposition to schizophrenia.

Many patients with schizophrenia experience spirituality as important, and it influences their attitudes toward medical treatment and helps them cope with challenging symptoms. However, the conception of psychosis as disorder is culture-specific, and influences public and personal attitudes and the unfavorable progression of symptoms.

Study details

Topics studied
Healthy Subjects

Study characteristics
Placebo-Controlled Double-Blind Within-Subject Randomized



Authors associated with this publication with profiles on Blossom

Amanda Feilding
Amanda is the Founder and Director of the Beckley Foundation. She's called the 'hidden hand' behind the renaissance of psychedelic science, and her contribution to global drug policy reform has also been pivotal and widely acknowledged.

Fernanda Palhano Xavier de Fontes
Fernanda Palhano Xavier de Fontes is a research engineer at the Brain Institute, UFRN. Her main areas of interest are psychedelics, psychiatry, and neuroimaging techniques such as fMRI and electroencephalography.

Luís Tófoli
Luís Tófoli is a professor at UNICAMP and one of the organizers of ICARO, his work is mostly done in Brazil and focused on ayahuasca.

Compound Details

The psychedelics given at which dose and how many times

LSD 50 μg | 1x